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Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes (Ribo-seq)

GSE268324 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/11/21 Platform GPL18573
Summary
The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation. We applied selective ribosome profiling to further investigate the determinants of CCR4-NOT recruitment to ribosomes in mammalian cells. This revealed that specific arginine codons in the P-site are strong signals for ribosomal recruitment of human CNOT3, a CCR4-NOT subunit. Cryo–electron microscopy and transfer RNA (tRNA) mutagenesis demonstrated that the D-arms of select arginine tRNAs interact with CNOT3 and promote its recruitment whereas other tRNA D-arms sterically clash with CNOT3. These effects link codon content to mRNA stability. Thus, in addition to their canonical decoding function, tRNAs directly engage regulatory complexes during translation, a mechanism we term P-site tRNA-mediated mRNA decay.
Published in
Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes
Zhu X, Cruz VE, Zhang H et al. · Science (New York, N.Y.) 2024 · PMID 39571015 · doi:10.1126/science.adq8587
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Also filed as BioProject PRJNA1116213 and SRA study SRP509804. Searching any of these in the dataset finder brings you back here.

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